Cancer Management and Research (Apr 2021)
MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis
Abstract
Jian Zheng,1 Xiaoxi Li,2 Cunwei Cai,3 Chengyu Hong,1 Bin Zhang4 1Department of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 2Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 3Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of ChinaCorrespondence: Jian ZhengDepartment of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, NO. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, People’s Republic of ChinaTel/ Fax +86-24-31916363Email [email protected]: The roles of microRNA (miR)-32 and miR-548a in non-small cell lung cancer (NSCLC) have been studied. But their influences on NSCLC cells to cisplatin (DDP) resistance remain elusive. This study estimated the mechanisms of miR-32 and miR-548a in NSCLC cells to DDP.Methods: Differentially expressed miRs in DDP-sensitive and resistant tissues were screened out using a GSE56036 chip. Then the predictive efficacies of miR-32 and miR-548a on DDP resistance were analyzed in NSCLC patients. The target mRNAs of miR-548a and miR-32 were predicted. miR-548a and miR-32 were knocked down to assess the influences of miR-32 and miR-548a on NSCLC growth. DDP-resistant cells were constructed and miR-32 and miR-548a expression was detected in resistant cells. After miR-32 and miR-548a knockdown, the IC50 value of DDP was detected. Then, the activation level of Wnt/β-catenin pathway was detected. The roles of miR-32 and miR-548a in NSCLC growth in vivo were detected by tumorigenesis experiment.Results: miR-32 and miR-548a were poorly expressed in DDP-resistant NSCLC. miR-32 and miR-548a mimic enhanced the DDP sensitivity of NSCLC cells. Both miR-32 and miR-548a targeted ROBO1, and overexpression of ROBO1 inhibited the promotion of miR-32 and miR-548a mimic on DDP sensitivity. ROBO1 activated the Wnt/β-catenin pathway, thus enhancing the DDP resistance.Conclusion: miR-32 and miR-548a target ROBO1 and inhibit Wnt/β-catenin activation, thus promoting the drug sensitivity of NSCLC cells to DDP.Keywords: non-small cell lung cancer, miR-32, miR-548a, cisplatin resistance, ROBO1, Wnt/β-catenin pathway
